The objective of the proposed studies is to develop a nonhuman primate model of heroin relapse to investigate the specific neuropharmacological mechanisms underlying the reinstatement of heroin-seeking behavior. High rates of relapse following periods of extended abstinence are typically experienced by many heroin users, further contributing to the challenge of long-term management of heroin addiction. The specific biological mechanisms, however, underlying this continued heroin-seeking behavior remain incompletely understood. Specific Aim 1 will further our knowledge of the regulation of heroin relapse via opioid receptor mechanisms by examining the effects of antagonists and agonists selective in binding to the mu and delta opioid receptors on heroin priming-induced reinstatement of heroin seeking. Specific Aim 2 will use a conceptually similar strategy to investigate the function of D1-like and D2-like dopamine receptor mechanisms in heroin reinstatement. Specific Aim 3 will seek to determine the ability of cocaine to reinstate heroin-seeking behavior, and the associated neurochemical mechanisms, in order to determine if priming-induced reinstatement generalizes to drugs that are often co-abused with heroin.